Several pharmacologic agents with differing actions have been associated with a syndrome characterized by phospholipid accumulation in body tissues in man and animals. These agents, which include chloroquine, diethylaminoethoxyhexestrol (DH), triparanol and chlorphenteramine, have common structural features and are referred to as cationic amphiphils. The goal of this project is to elucidate the molecular basis for the tissue phospholipid accumulation. In addition, a specific lysosomal phospholipid increases to a much greater degree than the other phospholipid classes. Another project goal is to determine the means of synthesis and degradation of this lysosomal phosphoglyceride, bis(monoacylglycero)phosphate (BMP). The role of the cationic amphiphils in BMP metabolism is under investigation. To date, our studies have shown that most of the increased phospholipid content of the liver of chloroquine or DH-treated rats can be attributed to the presence of large numbers of multilamellar cytoplasmic bodies or "myelin figures". These structures have been isolated in nearly pure form and the lipid content and enzymatic properties have been determined. These strctures, which are the hallmark of drug-induced lipidosis are rich in phospholipids, especially BMP, and in cholesterol (free and esterified). BMP synthesis has been demonstrated in the multilamellar bodies which have been shown to be of lysosomal origin based on their content of acid hydrolases.